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Sympathetic nervous system modulates the ocular hypotensive action of MT 2 ‐melatonin receptors in normotensive rabbits
Author(s) -
AlarmaEstrany Pilar,
Crooke Almudena,
Mediero Aránzazu,
Peláez Teresa,
Pintor Jesús
Publication year - 2008
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2008.00618.x
Subject(s) - melatonin , endocrinology , medicine , receptor , agonist , intraocular pressure , sympathetic nervous system , adrenergic receptor , forskolin , chemistry , luzindole , pharmacology , melatonin receptor , biology , blood pressure , ophthalmology
The aim of this study was to investigate the hypotensive effect of the melatonin analogue, N ‐butanoyl‐2‐(2‐methoxy‐6H‐isoindolo[2,1‐a]indol‐11‐yl)ethanamine (IIK7), through MT 2 ‐melatonin receptors and the involvement of the sympathetic nervous system in this action in New Zealand rabbit eyes. The topical application of melatonin or IIK7 produced a reduction in intraocular pressure of 20.2 ± 5.3% and 38.5 ± 3.2% respectively. This effect was concentration‐dependent; it was blocked by selective MT 2 receptor antagonists and was severely diminished after chemical sympathectomy. Immunohistochemistry and western blot analysis showed the ciliary processes as the site of this action and no co‐localization of MT 2 ‐melatonin receptor with the sympathetic nervous system was observed. The β‐adrenergic agonists, terbutaline and salbutamol, potentiated the hypotensive effect of IIK7 reducing intraocular pressure (IOP) 41.75 ± 4.26% and 44.7 ± 5.6% respectively. Also, IIK7 in presence of the nonspecific protein phosphatase inhibitor okadaic acid, lowered IOP 32.2 ± 4.5% and in presence of forskolin plus 3‐isobutyl‐1‐methylxanthine decreased IOP in 32.2 ± 5.47%. These data suggest that the melatonin agonist IIK7 reduces intraocular pressure by acting through MT 2 ‐melatonin receptors presumably decreasing aqueous humour formation. Also, in the presence of β‐adrenoceptor agonists MT 2 ‐melatonin receptors activity increase their ability to reduce IOP.